Techniques to Improve Efficacy of Second Trimester Medical Termination

NCT ID: NCT00864799

Last Updated: 2013-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 302 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2013-03-31

Brief Summary

Interruption of a pregnancy after 14 weeks gestation may be required when the fetus is dead, severely malformed or in cases of maternal illness. This process is usually conducted medically in Australia, using the synthetic prostaglandin E1 analogue misoprostol. This prostaglandin, although not licensed for use in pregnancy termination, is now a common abortifacient with a large accumulated experience both within Australia and internationally. Since 1996, misoprostol has been used at King Edward Memorial Hospital as the principal agent for second trimester pregnancy termination.

Misoprostol may be administered vaginally, orally, sublingually or buccally in the process of pregnancy termination. Each route of administration has its own advantages and disadvantages. The most appropriate route of administration, with the shortest duration of abortion and lowest side-effect profile has not been determined for all circumstances.

The combination of mifepristone and misoprostol is an established and effective method for second trimester pregnancy termination. Prior studies have demonstrated a significant reduction in the duration of abortion with misoprostol when mifepristone priming is used. In November 2007, the TGA (Therapeutic Goods Administration) approved an application by the Principal Investigator of this planned study for Authorised Prescriber status for use of the antiprogesterone agent mifepristone. Since January 2008 the combination of mifepristone and misoprostol has been used at KEMH for first and second trimester pregnancy termination of pregnancy, predominantly for circumstances of severe fetal abnormality.

There is however limited data on the impact of gestation on the duration of second trimester termination. Almost all published studies to date have recruited women in the early second trimester (typically with a median of 16 weeks gestation). However, most terminations of pregnancy for fetal abnormality (the most frequent reason for pregnancy interruption of a live fetus at KEMH) occur at 18-24 weeks gestation. The investigators' experience indicates a significant impact of increasing gestation with prolongation of the duration of pregnancy termination. In this study the investigators aim to evaluate three misoprostol regimens for second trimester pregnancy termination following mifepristone priming with the primary intention to develop a protocol which results in a delivery rate within 24 hours for 95% of women at gestations <24 weeks.

Secondary aims of this study will be to assess the incidence of maternal side-effects for each of the three regimens, the placental retention rates and the need for curettage for retained placental tissue. As the investigators will be using 3 different methods of misoprostol administration, the investigators will also review women's satisfaction with the three regimens for pregnancy termination.

Detailed Description

Aims:

1. To compare the efficacy of the vaginal and sublingual administration of the synthetic prostaglandin misoprostol with the currently used vaginal administration route in second trimester pregnancy termination.

2. To compare the impact of gestation of the duration of abortion within these three misoprostol regimens.

3. To compare the incidence of maternal side-effects between the three routes of prostaglandin administration.

4. To compare the incidence of placental retention and need for curettage between the three groups

Conditions

Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vaginal misoprostol

Women allocated to the vaginal misoprostol management protocol will receive a loading dose of 800 mcg misoprostol vaginally followed in 4 hours by 400 mcg vaginal misoprostol, the latter repeated every 4 hours for a maximum of 4 doses.

If abortion does not occur within 24 hours of commencement of this regimen, the sequence will be repeated.

If delivery is not accomplished within 48 hours of prostaglandin commencement, a transcervical Foley catheter will be inserted and a solution of prostaglandin F2 alpha infused 2-hourly until delivery occurs.

Group Type: ACTIVE_COMPARATOR

Misoprostol

Intervention Type: DRUG

Comparison of 3 routes of administration of misoprostol for termination of pregnancy 14-24 weeks

Oral misoprostol

Women allocated to the standard management protocol will receive a loading dose of 800 mcg misoprostol vaginally followed in 3 hours by 400 mcg misoprostol orally, the latter repeated every 3-hours to a maximum of 4 oral doses.

If abortion does not occur within 24 hours of commencement of this regimen, the sequence will be repeated.

If delivery is not accomplished within 48 hours of prostaglandin commencement, a transcervical Foley catheter will be inserted and a solution of prostaglandin F2 alpha infused 2-hourly until delivery occurs.

Group Type: ACTIVE_COMPARATOR

Misoprostol

Intervention Type: DRUG

Comparison of 3 routes of administration of misoprostol for termination of pregnancy 14-24 weeks

Sublingual misoprostol

Women allocated to the sublingual misoprostol protocol will receive a loading dose of 800 mcg misoprostol vaginally followed in 3 hours by 400 mcg sublingual misoprostol, the latter repeated every 3 hours for a maximum of 4 doses.

If abortion does not occur within 24 hours of commencement of this regimen, the sequence will be repeated.

If delivery is not accomplished within 48 hours of prostaglandin commencement, a transcervical Foley catheter will be inserted and a solution of prostaglandin F2 alpha infused 2-hourly until delivery occurs.

Group Type: ACTIVE_COMPARATOR

Misoprostol

Intervention Type: DRUG

Comparison of 3 routes of administration of misoprostol for termination of pregnancy 14-24 weeks

Interventions

Misoprostol

Comparison of 3 routes of administration of misoprostol for termination of pregnancy 14-24 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 14-24 weeks pregnant
• planned medical termination
• able to speak and understand English
• no contraindication to prostaglandins

Exclusion Criteria

• gestation < 13 weeks
• allergy/contraindication to misoprostol
• allergy/contraindication to mifepristone
• fetal demise

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

King Edward Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jan Dickinson

Professor Maternal Fetal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jan E Dickinson, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Western Australia

Locations

King Edward Memorial Hospital

Perth, Western Australia, Australia

Countries

Australia

References

Dickinson JE, Jennings BG, Doherty DA. Mifepristone and oral, vaginal, or sublingual misoprostol for second-trimester abortion: a randomized controlled trial. Obstet Gynecol. 2014 Jun;123(6):1162-1168. doi: 10.1097/AOG.0000000000000290.

Reference Type: DERIVED

PMID: 24807339 (View on PubMed)

Other Identifiers

1624/EW

Identifier Type: -

Identifier Source: org_study_id